Miniaturized assembly and method of filling assembly

• US 7,459,315 B2
• Filed: 04/25/2002
• Issued: 12/02/2008
• Est. Priority Date: 04/17/1997
• Status: Expired due to Fees

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated), United States Department Of Health And Human Services
• Original Assignee: Cytonix Corporation (Thermo Fisher Scientific Incorporated), United States Department Of Health And Human Services
• Inventors: Brown, James F
• Primary Examiner(s): Chin; Christopher L.
• Application Number:
  US10/131,854
• Publication Number:
  US 20020164820A1
• Time in Patent Office: 2,413 Days
• Field of Search: 422/50, 422/57, 422/58, 435/287.1, 435/287.2, 435/288.3, 435/288.7, 436/164, 436/172, 436/518, 436/524, 436/527, 436/531, 436/809
• US Class Current: 436/518
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00644 the porous medium being present in discrete locations, e.g. gel pads
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 2200/06 Fluid handling related problems
• CPC Class Codes: B01L 2200/0642 Filling fluids into wells by specific techniques
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: B01L 3/50851 specially adapted for heating or cooling samples laboratory heating apparatus B01L7/00; incubators C12M
• CPC Class Codes: B01L 3/5088 confining liquids at a location by surface tension, e.g. virtual wells on plates, wires B01L3/50857 takes precedence
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12Q 1/6806 Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6844 : Nucleic acid amplification reactions
• CPC Class Codes: C12Q 1/686 : Polymerase chain reaction [PCR]
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: Y10S 436/805 : Optical property
• CPC Class Codes: Y10S 436/809 : Multifield plates or multicontainer arrays
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A miniaturized assembly is provided whereby a fluid sample can be divided into a plurality of sample portions in retaining wells and the sample fluid can be displaced from open ends of the wells while simultaneously being sealed in the wells. A method of dividing a fluid sample using the assembly is also provided.

Claims

1. A method for dividing a chemical or biological fluid sample into a plurality of sample portions and simultaneously sealing said plurality of sample portions against contamination and evaporation, said method comprising:

introducing a chemical or biological fluid sample into an assembly, said assembly comprising a first member, said first member comprising a substrate and a plurality of sample chambers formed in or on said substrate,

said substrate having at least one substrate surface,

each of said sample chambers having an open end and having at least one sample chamber surface,

a surface property of at least a first of said sample chamber surfaces differing from a surface property of said substrate surface, such that said fluid sample has a first affinity to said first sample chamber and a second affinity to said substrate surface, said first affinity differing from said second affinity; and

then

introducing a displacing fluid into said assembly, said displacing fluid being immiscible with said fluid sample, thereby displacing said fluid sample away from the open end of each of said plurality of sample chambers and simultaneously sealing the open end of each of said plurality of sample chambers.

2. A method as recited in claim 1, wherein said displacing fluid comprises a curable adhesive.

3. A method as recited in claim 2, further comprising curing the curable adhesive after said displacing.

4. A method as recited in claim 1, wherein said surface property of said first sample chamber surface and said surface property of said substrate surface comprise surface chemistries.

5. A method as recited in claim 1, wherein said assembly further comprises a second member, a channel being defined between said second member and said first member, said channel communicating with said sample chambers, said fluid sample being introduced into said channel during said introducing a fluid sample, and said displacing fluid being introduced into said channel during said introducing a displacing fluid.

6. A method as recited in claim 1, wherein at least one of said sample chambers has a volume of about 1 picoliter or less.

7. A method as recited in claim 1, wherein at least one of said sample chambers has a volume in the range of from about 1 picoliter to about 1 microliter.

8. A method as recited in claim 1, wherein at least one of said sample chambers has a volume of about 1 nanoliter.

9. A method as recited in claim 1, wherein said fluid sample has a volume of about 1 picoliter or less.

10. A method as recited in claim 1, wherein said fluid sample has a volume in the range of from about 1 picoliter to about 1 microliter.

11. A method as recited in claim 1, wherein said fluid sample has a volume of about 1 nanoliter or less.

12. A method for dividing a chemical or biological fluid sample into a plurality of sample portions and simultaneously sealing said plurality of sample portions against contamination and evaporation, said method comprising:

introducing a chemical or biological fluid sample into an assembly, said assembly comprising a plate and a first element positioned on said plate, a plurality of sample chambers being formed in or through said first element, each of said sample chambers having an open end, each of said sample chambers having at least one sample chamber surface;

a surface property of at least a first of said sample chamber surfaces differing from a surface property of said plate, such that said fluid sample has a first affinity to said first sample chamber surface and a second affinity to said plate, said first affinity differing from said second affinity; and

then

introducing a displacing fluid into said assembly, said displacing fluid being immiscible with said fluid sample, thereby displacing said fluid sample away from the open end of each of said plurality of sample chambers and simultaneously sealing the open end of each of said plurality of sample chambers.

13. A method as recited in claim 12, wherein said displacing fluid comprises a curable adhesive.

14. A method as recited in claim 13, further comprising curing the curable adhesive after said displacing.

15. A method as recited in claim 12, wherein said assembly further comprises an opposite member, a channel being defined between said opposite member and said plate, said channel communicating with said sample chambers, said fluid sample being introduced into said channel during said introducing a fluid sample, and said displacing fluid being introduced into said channel during said introducing a displacing fluid.

16. A method as recited in claim 12, wherein said surface property of said first sample chamber surface and said surface property of said plate comprise surface chemistries.

17. A method as recited in claim 12, wherein at least one of said sample chambers has a volume of about 1 picoliter or less.

18. A method as recited in claim 12, wherein at least one of said sample chambers has a volume in the range of from about 1 picoliter to about 1 microliter.

19. A method as recited in claim 12, wherein at least one of said sample chambers has a volume of about 1 nanoliter.

20. A method as recited in claim 12, wherein said fluid sample has a volume of about 1 picoliter or less.

21. A method as recited in claim 12, wherein said fluid sample has a volume in the range of from about 1 picoliter to about 1 microliter.

22. A method as recited in claim 12, wherein said fluid sample has a volume of about 1 nanoliter or less.

23. A method for dividing a chemical or biological fluid sample into a plurality of sample portions and simultaneously sealing said plurality of sample portions against contamination and evaporation, said method comprising:

introducing a chemical or biological fluid sample into an assembly, said assembly comprising a first member, said first member comprising a substrate and a plurality of sample chambers formed in or on said substrate,

said substrate having at least one substrate surface,

each of said sample chambers having an open end having at least one sample chamber surface,

introducing a displacing fluid into said assembly, said displacing fluid being immiscible with said fluid sample, thereby displacing said fluid sample away from the open end of each of said plurality of sample chambers and simultaneously sealing the open end of each of said plurality of sample chambers.

24. A method for dividing a chemical or biological fluid sample into a plurality of sample portions and simultaneously sealing said plurality of sample portions against contamination and evaporation, said method comprising:

introducing a chemical or biological fluid sample into an assembly, said assembly comprising a substrate comprising first regions and second regions, a surface property of at least a first of said second regions differing from a surface property of said first regions, such that said fluid sample has a first affinity to said first regions and a second affinity to at least one of said second regions, said first affinity differing from said second affinity; and

then

introducing a displacing fluid into said assembly, said displacing fluid being immiscible with said fluid sample, thereby displacing said fluid sample away from surfaces of said second regions and simultaneously sealing said second regions.